Dr Pierre Dilda

Bio

Research Interests:

Overcoming the acquired or innate chemotherapy resistance of malignant tumours has been an ongoing challenge ever since the development of the first chemotherapeutic agents.

The discovery that arsenic trioxide induces complete remission in a high percentage of patients with acute promyelocytic leukaemia has renewed interest in arsenic for the treatment of cancer. Organic arsenicals are currently being investigated in cancer therapy due to their generally better toxicity profile compared to inorganic derivatives. Dr Dilda has specialised in organic arsenical anti-cancer compounds.

GSAO (4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide), an arsenic-based GSH-conjugate, is a mitochondrial poison that inhibits proliferating, but not growth-quiescent, endothelial cells in vitro and angiogenesis in vivo. It demonstrated anti tumor activity evaluated in clinical. For GSAO, extracellular γGT activity is an essential and limiting step in its activation into membrane permeable compounds. Indeed, it has recently been demonstrated that tumor γGT could be used for therapeutic delivery.

PENAO, (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid), a second generation compound, shares the same mitochondrial molecular target as GSAO. PENAO, 20-fold more potent than GSAO, demonstrates both in vitro and in animal models anti-proliferative and anti-angiogenic activities. The combination of these two properties leads to strong anti-tumour activity. Interestingly, PENAO has a strong anti-proliferative activity against glioblastoma cell lines and primary isolates of diffuse intrinsic pontine glioma. In vivo, PENAO demonstrated preclinical activity without signs of toxicity in tumor models of glioblastoma, pancreatic carcinoma and ovarian carcinoma. PENAO is currently tested in clinical Phase I/IIa in patients with solid tumours refractory to standard chemotherapy. Our recent work demonstrated that when combined with other drugs such as mTOR and EGFR inhibitors, PENAO anti-tumour activity is massively enhanced notably on drug resistant tumour cells. This discovery offers valuable options to the clinicians for the design of PENAO clinical Phase II.

We have recently characterised a novel polyarsenic adamantane-type class of compounds. The potency of the novel polyarsenic adamantane-type class of compounds was demonstrated in three types of drug resistant cancers. These compounds, not affected by resistance mechanisms responsible for the failure of cancer chemotherapeutics, are notably a hope for the treatment of cancers with a poor overall survival.

Dr Dilda's research has been published in the top 3 cancer biology journals such as Cancer Cell,Journal of the National Cancer Institute andCancer Researchand was the subject of commentaries in Nature Reviews Cancer andScience-Business eXchange.